The major objective of this proposal is to determine the efficacy of liposomal MTP ([L-MTP-PE] a monocyte/macrophage activator) in controlling or preventing lung metastases in patients with osteosarcoma who have relapsed on chemotherapy. The majority of children who present with osteosarcoma have undetectable pulmonary micrometastases. Despite surgical resection of the primary tumor plus adjuvant chemotherapy the metastases free survival (MFS) at 2 yrs is 66%. The majority of patients who develop pulmonary metastases do so while receiving chemotherapy. These patients have a poor prognosis. Although they can be rendered "disease free" by surgery, the recurrence rate is 60-70% within 1 year. Salvage chemotherapy has had little effect on the MFS of these individuals. Our proposal is to employ L-MTP-PE therapy in a phase II trial in this group of patients. The goal is to activate the body's monocytes and pulmonary macrophages to eradicate the residual micrometastases that we know exist in the lungs. The activation of monocyte tumoricidal properties was demonstrated in 20 of 28 patients receiving i.v. L-MTP-PE in a phase I trial. This activity correlated with IL-1 secretion. Following the surgical removal of visible pulmonary metastases, patients will receive L-MTP-PE twice a wk. for 3 mo. (no other therapy). Relapse rates will be compared to historical controls. Serum IL-1, TNF and IL-6 levels will be monitored as well as monocyte tumoricidal activity, monocyte membrane IL-1 and TNF, and monocyte IL-1 and TNF secretion, pre, during and post L-MTP-PE. In addition normal monocytes will be incubated with L-MTP-PE. The secretion and mRNA expression of IL-1, TNF and IL-6 will be monitored over time to determine which cytokine(s) is induced first and which, if any, are stimulated secondarily. These laboratory studies will help to elucidate the mechanism of action of L-MTP-PE. The proposed clinical and laboratory studies together should lay the ground work for future adjuvant trials using L-MTP-PE in the treatment of osteosarcoma and other malignancies.